title: Long acting propranolol and HSP-70 rich tumor lysate reduce tumor growth and enhance immune response against fibrosarcoma in Balb/c mice.
abstract: BACKGROUND
  Noradrenaline (NA), the principal neurotransmitter released from sympathetic nerve terminals, influences T-cell maturation, not only directly in developing T cells, but also indirectly, by acting on the thymic nonlymphoid cells. In vitro and in vivo studies have demonstrated the anti-proliferative, anti-migratory, anti-angiogenic and cytotoxic properties of propranolol, β-AR blocker, against various cancers.
  
  
  OBJECTIVE
  To evaluate the effect of propranolol on efficacy of HSP-70 rich lysate vaccine in immunotherapy of fibrosarcoma.
  
  
  METHODS
  Mouse fibrosarcoma WEHI-164 cells were used to immunize tumor-bearing mice with or without propranolol and HSP-70. Splenocytes proliferation, cytotoxicity activity of the splenocytes, naturally occurring CD4+ CD25high T-reg cells and IFN-γ and IL-4 secretion as well as tumor size, were assessed to describe the anti-tumor immune response.
  
  
  RESULTS
  A significant increase in the level of IFN-γ in the mice vaccinated with WEHI-164 cells enriched with HSP-70 and co-treated with propranolol was observed compared to controls. However, HSP enrichment or propranolol treatment alone did not enhance the immune response as measured by the level of IFN-γ. Likewise, a decrease in tumor growth in the test group (p<0.01) and a significant increase in CTL activity (p<0.05) was observed.
  
  
  CONCLUSIONS
  HSP enriched vaccine shows anti-tumor activity, probably due to the modulation of immune responses.
authors.affiliation: Department of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Khalili
authors.forename: Zuhair Muhammad
authors.initials: ZM
authors.lastname: Hassan
authors.forename: Shahram
authors.initials: S
authors.lastname: Shahabi
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Pourfathollah
authors.forename: Seyed Nasser
authors.initials: SN
authors.lastname: Ostad
authors.forename: Shokoofe
authors.initials: S
authors.lastname: Noori
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mahdavi
authors.forename: Habib
authors.initials: H
authors.lastname: Haybar
authors.forename: Ladan
authors.initials: L
authors.lastname: Langroudi
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002457:Cell Extracts / Q000008:administration & dosage; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology / Q000628:therapy*; D018840:HSP70 Heat-Shock Proteins / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D011433:Propranolol / Q000008:administration & dosage*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D019496:Cancer Vaccines; D002457:Cell Extracts; D018840:HSP70 Heat-Shock Proteins; D015847:Interleukin-4; D007371:Interferon-gamma; D011433:Propranolol; D009638:Norepinephrine